Interferon-induced inhibition

Most of the cell-free extracts used in these studies had been pre-incubated to reduce the translation of endogenous mRNA. Since different preparations of lysates exhibited varying degrees of interferon-induced inhibition, we studied the influence of the length of time of pre-incubation on the interferon-induced inhibition of vitro protein synthesis. e could establish that the ability of cell-free extracts to translate mengo virus RNA was a function of the time of pre-incubation. The ability of an extract from interferon-treated (int. S-10) cells to translate mengo virus RNA was not impaired when compared with an extract from control cells until between 60 and 90 of pre-incubation. At this point, although the activity of the control extract declined somewhat, the activity of the Int. S-10 declined much more rapidly. 

In marked contrast with mengo virus RNA, poly (lJ,C) translation was essentially unaffected by the addition of dsRNA to cell-free extracts from interferon-treated cells and in the presence of dsRNA, tRNA was still able to reverse the interferon-induced inhibition apparent in extracts pre-incubated for 75 (Table 4) Thus, with two doses of poly(l) poly(C), which gave 80% inhibition of mengo RNA translation in interferon-treated cell extracts pre-incubated for 15 min, only a slight effect (12%) on poly (U,C) translation was observed. After pre-incubation for 75 min, translation of poly (lJ,C) by the interferon-treated cell extract was... 

Interferons (lENs) (52,53), a family of species-specific vertebrate proteins, confer nonspecific resistance to a broad range of viral infections, affect cell proliferation, and modulate immune responses. AH three principal interferons, a-interferon (lEN-a) produced by blood leucocytes, P-interferon (lEN-P) by fibroblasts, and y-interferon (lEN-y) by lymphocytes, also have antiviral activity. The abiUty of interferons to inhibit growth of transplantable and carcinogen-induced tumor led to research showing the direct antiproliferative and indirect immune-mediated antitumor activities (see Chemotherapeutics, anticancer). IENs have been found to be efficacious in certain malignancies and viral infections, eg, hairy cell leukemia (85% response) and basal cell carcinoma (86% response). However, the interferons do have adverse side effects (54). 

Type I interferons induce a vims-resistant state in human cells, whereas Type II are more active in inhibiting growth of tumour cells. 

Kurzrock R, Rohde MF, Quesada JR, Gianturco SH, Bradley WA, Sherwin SA, Gutterman JU. Recombinant gamma interferon induces hypertriglyceridemia and inhibits post-heparin lipase activity in cancer patients. J Exp Med 1986 164(4) 1093-101. 

Frohman EM, Vayuvegula B, Gupta S, van den Noort S (1988) Norepinephrine inhibits gamma-interferon-induced major histocompatibility class II (la) antigen expression on cultured astrocytes via beta-2-adrenergic signal transduction mechanisms. Proc. Natl. AcadSci. USA 85 1292-1296. 

Sarris, A. H., Broxmeyer, H. E., Wirthmueller, U., Karasavvas, N., Cooper, S., Lu, L., Krueger, J., and Ravetch, J. V. (1993) Human interferon-inducible protein 10 expression and purification of recombinant protein demonstrate inhibition of early human hematopoietic progenitors. J. Exp. Med. 178,1127-1132. 

Administration of cycloheximide (60 mg/kg) 1 hr prior to tilorone administration inhibited the interferon response43,44. The inhibition by cycloheximide suggested that protein synthesis was involved in the appearance of interferon in the serum. For a more complete discussion of interferon induction, see the review on synthetic interferon inducers written by DeClercq45. ... 

Inhibition of prostaglandin, thromboxane and leukotriene biosynthesis. 15. Ill Integrated control of trematode diseases. 12. 53 Interethnic factors affecting drug response. 25. 1 Interferon and interferon inducers. 10, 101... 

Interferon and interferon inducers significantly inhibit Bunya virus infections in animal models (60). As an adjunct to ribavirin, interferon gamma is promising for the treatment of Arena virus infections (48). There are no other antiviral agents available for treatment of VHF infections (48). 

Aronica SM, Mantel C, Gonin R, et al. Interferon-inducible protein 10 and macrophage inflammatory protein-1 alpha inhibit growth factor stimulation of Raf-1 kinase activity and protein synthesis in a human growth factor-dependent hematopoietic cell line. J Biol Chem 1995 270 21998-2007. 

Sgadari C, AngioliUo AL, Tosato G. Inhibition of angiogenesis by interleukin-12 is mediated by the interferon-inducible protein 10, Blood 1996 87 3877-82. 

Feldman AL, Friedl J, Lans TE, Libutti SK, Lorang D, Miller MS, Turner EM, Hewitt SM, Alexander HR. Retroviral gene transfer of interferon-inducible protein 10 inhibits growth of human melanoma xenografts. Int. J. Cancer 99 149-153, 2002. 

Addison, C.L., D.A. Arenberg, S.B. Morris, Y.Y. Xue, M.D. Burdick, M.S. Mulligan, M.D. Iannettoni, and R.M. Strieter. The CXC chemokine, monokine induced by interferon-gamma, inhibits non-small cell lung carcinoma tumor growth and metastasis. Hum Gene Ther 11 247-61, 2000. 

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